Autologous bone marrow–derived cells for venous leg ulcers treatment: a pilot study

Otero, Gabriela; Agorio, Caroline; Sujanov, A.; Echarte, L.; Tchekmedyian, A.; Montelongo, M.D.C.; Menyou, Alba; Rodríguez, Andrés; Díaz, Lilián; Rodríguez, Ismael; Touriño, Cristina

doi:10.1016/j.jcyt.2019.01.002

Cited by 8 publications

(8 citation statements)

References 49 publications

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“…The bone marrow was harvested, processed, and injected in the periulcer bed. At 12-month follow-up, the wound area had decreased and pain had improved [176]. Another pilot trial evaluating progenitor cells obtained from adipose tissue was conducted in 8 treated and 8 control VLU patients.…”

Section: Latest Innovations In Surgical Treatment and Drug Therapiesmentioning

confidence: 99%

Why Venous Leg Ulcers Have Difficulty Healing: Overview on Pathophysiology, Clinical Consequences, and Treatment

Raffetto

Ligi

Maniscalco

et al. 2020

JCM

148

114

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Venous leg ulcers (VLUs) are one of the most common ulcers of the lower extremity. VLU affects many individuals worldwide, could pose a significant socioeconomic burden to the healthcare system, and has major psychological and physical impacts on the affected individual. VLU often occurs in association with post-thrombotic syndrome, advanced chronic venous disease, varicose veins, and venous hypertension. Several demographic, genetic, and environmental factors could trigger chronic venous disease with venous dilation, incompetent valves, venous reflux, and venous hypertension. Endothelial cell injury and changes in the glycocalyx, venous shear-stress, and adhesion molecules could be initiating events in VLU. Increased endothelial cell permeability and leukocyte infiltration, and increases in inflammatory cytokines, matrix metalloproteinases (MMPs), reactive oxygen and nitrogen species, iron deposition, and tissue metabolites also contribute to the pathogenesis of VLU. Treatment of VLU includes compression therapy and endovenous ablation to occlude the axial reflux. Other interventional approaches such as subfascial endoscopic perforator surgery and iliac venous stent have shown mixed results. With good wound care and compression therapy, VLU usually heals within 6 months. VLU healing involves orchestrated processes including hemostasis, inflammation, proliferation, and remodeling and the contribution of different cells including leukocytes, platelets, fibroblasts, vascular smooth muscle cells, endothelial cells, and keratinocytes as well as the release of various biomolecules including transforming growth factor-β, cytokines, chemokines, MMPs, tissue inhibitors of MMPs (TIMPs), elastase, urokinase plasminogen activator, fibrin, collagen, and albumin. Alterations in any of these physiological wound closure processes could delay VLU healing. Also, these histological and soluble biomarkers can be used for VLU diagnosis and assessment of its progression, responsiveness to healing, and prognosis. If not treated adequately, VLU could progress to non-healed or granulating VLU, causing physical immobility, reduced quality of life, cellulitis, severe infections, osteomyelitis, and neoplastic transformation. Recalcitrant VLU shows prolonged healing time with advanced age, obesity, nutritional deficiencies, colder temperature, preexisting venous disease, deep venous thrombosis, and larger wound area. VLU also has a high, 50–70% recurrence rate, likely due to noncompliance with compression therapy, failure of surgical procedures, incorrect ulcer diagnosis, progression of venous disease, and poorly understood pathophysiology. Understanding the molecular pathways underlying VLU has led to new lines of therapy with significant promise including biologics such as bilayer living skin construct, fibroblast derivatives, and extracellular matrices and non-biologic products such as poly-N-acetyl glucosamine, human placental membranes amnion/chorion allografts, ACT1 peptide inhibitor of connexin 43, sulodexide, growth factors, silver dressings, MMP inhibitors, and modulators of reactive oxygen and nitrogen species, the immune response and tissue metabolites. Preventive measures including compression therapy and venotonics could also reduce the risk of progression to chronic venous insufficiency and VLU in susceptible individuals.

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Section: Latest Innovations In Surgical Treatment and Drug Therapiesmentioning

confidence: 99%

Why Venous Leg Ulcers Have Difficulty Healing: Overview on Pathophysiology, Clinical Consequences, and Treatment

Raffetto

Ligi

Maniscalco

et al. 2020

JCM

148

114

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“…MSCs have gained considerable attention as promising therapeutic agents for treating chronic wounds. Previous studies and clinical trials have demonstrated that MSCs from bone marrow and adipose tissue are capable of promoting cutaneous wound healing in animals [25][26][27] and patients with chronic wounds [28,29]. MSCs isolated from the umbilical cord (Wharton's jelly) may also become a perspective therapeutic agent for long-term nonhealing wounds.…”

Section: Discussionmentioning

confidence: 99%

“…Hence, UCMSC therapy could be qualified as a safe treatment procedure. Previous clinical studies examining the effectiveness of MSC therapy in patients with various acute and chronic skin injuries such as diabetic skin ulcers, radiation, and thermal burns have shown the improvement of the wounds within days following administration of MSCs, characterized by a decrease in wound size, increase in the vascularity of the dermis, and increased dermal thickness of the wound bed [28,29,38,39]. The type of MSCs used for chronic wound therapy in these studies varies widely: cultured MSCs from bone marrow and adipose tissue, bone marrow mononuclear cells, and stromal vascular fraction derived from adipose tissue.…”

Section: Discussionmentioning

confidence: 99%

Locally Delivered Umbilical Cord Mesenchymal Stromal Cells Reduce Chronic Inflammation in Long-Term Nonhealing Wounds: A Randomized Study

Suzdaltseva

Zhidkih

Kiselev

et al. 2020

Stem Cells International

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Inflammation is part of a complex biological response to injury that mediates a rapid mobilization of cells and triggers the restoration of tissue homeostasis. The systemic diseases of the connective tissues, repetitive strain injuries, neuropathy, and vascular impairment lead to the development of a chronic inflammatory state. In such cases, a forced intervention is required to trigger tissue regeneration. Mesenchymal stromal cells (MSCs) have been considered a perspective tool for regenerative medicine because of their ability to change the expression and secretory profile under the influence of signals from the microenvironment to perform a regulatory function at the site of tissue damage. In this study, MSCs were isolated from the human umbilical cord (UCMSCs). The ability of UCMSCs to regulate chronic inflammation was investigated in a randomized placebo-controlled pilot study to assess the efficacy and safety of UCMSC therapy in patients with nonhealing wounds. A total of 108 patients with chronic wounds of different etiologies were randomly divided into two groups according to the criteria of inclusion and exclusion. The group (n=59) that was treated with a single local subcutaneous infusion of UCMSCs around the wound periphery showed a pronounced growth of granulation tissue, improved blood microcirculation, and reduction in wound size compared to the placebo group (n=49). No prominent adverse events were detected in patients from the UCMSC group during the 1-year follow-up period. This research has demonstrated that locally delivered allogeneic UCMSCs can contribute to chronic wound repair and provide an additional support toward new therapeutic strategies. Registration certificate №FS2006/341 was issued by the Federal Service for Surveillance in Healthcare.

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“…Both ulcer size and wound pain were significantly reduced 12 months after BMDC treatment, and a long-term follow-up showed that treatment was safe and well tolerated. Despite the low number of patients studied, these data have shown that autologous BMDC treatment could be a useful, feasible, and safe procedure to enhance ulcer healing [ 85 ].…”

Section: Current Researchmentioning

confidence: 99%

Chronic Leg Ulcers: Are Tissue Engineering and Biomaterials Science the Solution?

et al. 2021

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Chronic leg ulcers (CLUs) are full thickness wounds that usually occur between the ankle and knee, fail to heal after 3 months of standard treatment, or are not entirely healed at 12 months. CLUs present a considerable burden on patients, subjecting them to severe pain and distress, while healthcare systems suffer immense costs and loss of resources. The poor healing outcome of the standard treatment of CLUs generates an urgent clinical need to find effective solutions for these wounds. Tissue Engineering and Biomaterials Science offer exciting prospects for the treatment of CLUs, using a broad range of skin substitutes or scaffolds, and dressings. In this review, we summarize and discuss the various types of scaffolds used clinically in the treatment of CLUs. Their structure and therapeutic effects are described, and for each scaffold type representative examples are discussed, supported by clinical trials. Silver dressings are also reviewed due to their reported benefits in the healing of leg ulcers, as well as recent studies on new dermal scaffolds, reporting on clinical results where available. We conclude by arguing there is a further need for tissue-engineered products specifically designed and bioengineered to treat these wounds and we propose a series of properties that a biomaterial for CLUs should possess, with the intention of focusing efforts on finding an effective treatment.

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Autologous bone marrow–derived cells for venous leg ulcers treatment: a pilot study

Cited by 8 publications

References 49 publications

Why Venous Leg Ulcers Have Difficulty Healing: Overview on Pathophysiology, Clinical Consequences, and Treatment

Why Venous Leg Ulcers Have Difficulty Healing: Overview on Pathophysiology, Clinical Consequences, and Treatment

Locally Delivered Umbilical Cord Mesenchymal Stromal Cells Reduce Chronic Inflammation in Long-Term Nonhealing Wounds: A Randomized Study

Chronic Leg Ulcers: Are Tissue Engineering and Biomaterials Science the Solution?

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